Accepted Manuscript Aedes and the triple threat of DENV, CHIKV, ZIKV – arboviral risks and prevention at the 2016 Rio Olympic games Mary E. Wilson, Patricia Schlagenhauf PII:

S1477-8939(16)00012-0

DOI:

10.1016/j.tmaid.2016.01.010

Reference:

TMAID 953

To appear in:

Travel Medicine and Infectious Disease

Received Date: 27 January 2016 Accepted Date: 27 January 2016

Please cite this article as: Wilson ME, Schlagenhauf P, Aedes and the triple threat of DENV, CHIKV, ZIKV – arboviral risks and prevention at the 2016 Rio Olympic games, Travel Medicine and Infectious Disease (2016), doi: 10.1016/j.tmaid.2016.01.010. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

EDITORIAL Aedes and the triple threat of DENV, CHIKV, ZIKV – arboviral risks and prevention at the 2016 Rio Olympic games

RI PT

Mary E. Wilson1, Patricia Schlagenhauf2 1. Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco; Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Corresponding author Email: [email protected]

SC

2. University of Zürich Centre for Travel Medicine, Institute for Epidemiology, Biostatistics and Prevention, WHO Collaborating Centre for Travellers’ Health, Zürich, Switzerland

EP

TE D

M AN U

This year Brazil will host the Olympic games in Rio de Janeiro, a magnificent city of six million (urban area with almost 12 million) that hugs the sea and encompasses stunning peaks, vast favelas, and the Tijuca Forest. Brazilians have also been serving as hosts for three invading viruses: dengue virus, which has caused epidemics of increasing size, geographic reach, and severity since the early 1980s, chikungunya virus since 2014, and Zika virus since April 2015. All four dengue serotypes currently circulate in Brazil. In 2015, almost 69,000 cases were reported in Rio de Janeiro state (incidence rate 417 per 100,000 population) [http://portalsaude.saude.gov.br/images/pdf/2016/janeiro/15/svs2016-be003-denguese52.pdf]. More than 20,000 suspected cases of chikungunya virus infection were reported in Brazil in 2015. Zika virus, formerly described as a virus causing a self-limited, nonspecific febrile illness with rash, aches, and conjunctivitis is now suspected of leaving a costly and devastating legacy: microcephaly in infants born to women infected during pregnancy. Guillain-Barre syndrome in Zika-infected individuals was observed in earlier outbreaks[1]. The Brazilian Zika epidemic, the largest recorded to date (estimated 440,000 to 1.3 million clinical cases), sadly means that studies assessing causality, level of risk, and risk factors may provide clear answers.

AC C

The flavivirus, Zika virus, was first isolated from a sentinel rhesus monkey in the Zika Forest in Uganda in 1947. Serologic and virologic evidence of human infection was found in many African and Asian countries in the latter half of the 20th century. After decades of desultory activity, the virus emerged causing a large epidemic on Yap Island (Federated States of Micronesia] in 2007 – the first spread outside of Africa and Asia. More than 100 residents had confirmed or probable infection. A serosurvey suggested that 73% of the population (of about 7000) had been infected [2] although only 18% had symptoms. Documentation of Zika virus infections in ill returned travelers in recent years, as well as occasional local cases have confirmed Zika presence in many Asian countries (e.g., Thailand, Philippines, Cambodia, Malaysia, Indonesia). Outbreaks in French Polynesia (2013-2014) were associated with an increase in Guillain-Barre syndrome [1]. Zika virus infections spread to Easter Island and local transmission has now expanded to at least 20 countries in the Western Hemisphere [www.cdc.gov/zika/, www.paho.org]. Zika virus has spread to 19 of 26 Brazilian states (including Rio de Janeiro) since local transmission was first documented in April 2015 in northeastern Brazil. An outbreak in

1

ACCEPTED MANUSCRIPT

Northeast Brazil was followed by a 20-fold increase in reported cases of microcephaly. Hampered by the lack of wide availability of good diagnostic tests and no requirement for reporting infections, officials lack information about the exact size and scope of the outbreak . Virologic studies show the Zika virus circulating in Bahia, Brazil is similar to the lineage that caused the outbreak in French Polynesia [3].

RI PT

Zika virus can cause a self-limited illness characterized by fever, rash, arthralgia, and conjunctivitis. In Rio de Janeiro hundreds of pregnant women have now reported having illness with “spots on the skin”. Although the story is still unfolding – and over-reporting may be common - between October 22, 2015 and January 2016 there were 3530 microcephaly cases reported in Brazil that were suspected to be related to Zika virus infections.

M AN U

SC

Not surprisingly, all recent outbreaks have occurred in areas that also have had dengue outbreaks. Zika virus and dengue viruses share the same mosquito vector, Aedes aegypti. The Asian tiger mosquito, Aedes albopictus, may also play a role as vector, but this remains to be documented. Zika virus is one of few arboviruses that potentially is transmitted sexually. A man likely transmitted Zika virus sexually to his wife. In another case Zika virus was recovered from semen from a man with hematospermia after recovery from a febrile illness [4].

EP

TE D

The triple threat also includes chikungunya virus, an alphavirus that has been carried around the globe, causing explosive outbreaks and leaving in its wake many with disabling joint symptoms that may persist for months or years. Brazil is host to chikungunya viruses of two genotypes, the Asian genotype (the virus circulating in most parts of the Americas) and the East, Central, South African (ECSA), which has the potential to undergo mutations that allow more efficient transmission by Aedes albopictus [5]. Chikungunya infections have been reported widely in Brazil; many have been diagnosed based on clinical and epidemiological criteria because of lack of widely available diagnostic tests. Although good diagnostic tests are available for dengue infections, many infections are not laboratory confirmed and underreporting is common. Underreporting and misdiagnosis of chikungunya and Zika virus infections are likely to be common until clinicians gain experience with the infections and have easy access to sensitive and specific diagnostic tests. Currently the diagnostic capacity for Zika virus is limited to a few reference laboratories. Dengue is reportable in Brazil but, at present, Zika and chikungunya infections are not.

AC C

A general estimate is that about only one in four dengue infections causes symptoms. Most studies find that the majority of chikungunya infections are symptomatic (50-85% symptomatic). The study in Yap found only 18% of those infected with Zika virus had symptoms [2]. Will men with asymptomatic Zika infection be able to transmit infection sexually? Asymptomatic infections with all three viruses have implications for blood donations and transfusion risk. The peak season for dengue transmission in Rio de Janeiro is February through June (especially March through May) although a low level of transmission continues throughout the year, including in travelers to Brazil, as documented in a study from the GeoSentinel Surveillance Network [6] and other [7]. The Olympic games and Paralympics will take place during August and September, the months least favorable for dengue transmission. Because the Zika and chikungunya viruses share the same mosquito vector as dengue, one might anticipate that more intense transmission would

2

ACCEPTED MANUSCRIPT

RI PT

occur during similar periods. Transmission dynamics could be different, however, for Zika or chikungunya viruses at first encounter with a completely susceptible population. The chikungunya virus outbreak in Feira de Santana, Brazil in 2014, for example, peaked at a time of year (August and September) that was not typical for dengue[5]. Investigators initially expected to find dengue virus but instead found chikungunya virus in this outbreak, with 1346 cases. The population in Brazil, including Rio de Janeiro, has extensive experience with dengue infections, but none with Zika and chikungunya viruses until recent outbreaks.

M AN U

SC

Based on viral sequencing data there appear to have been at least 2 introductions of chikungunya viruses into Brazil that sparked autothchonous transmission – one from the Caribbean (Asian genotype) and one in a Brazilian returning from Angola (ECSA genotype). Both have spread in Brazil. Although all three viruses – dengue, chikungunya, and Zika - originally spilled over into the human population from an animal host, none of the three viruses is known to have an animal intermediate host or reservoir within Brazil. It remains to be seen whether an animal reservoir becomes established within Brazil In Salvador, Bahia in 2015 the simultaneous circulation of dengue (DENV1 and DENV4), chikungunya, and Zika viruses was documented [8]. All three infections have been transmitted in Rio de Janeiro, but so far numbers are small for chikungunya and Zika viruses. Another flavivirus, yellow fever virus, also transmitted by the same vectors, is endemic in large areas of Brazil in a sylvatic cycle, but wide use of the vaccine by Brazilians and visitors to endemic areas has prevented most cases and deaths.

EP

TE D

Each virus can cause a self limited acute febrile illness, with muscle aches and rash. The similarities mean that sensitive and specific diagnostic tests will need to be readily available and good surveillance in place. But each has unique features: acute dengue infection is complicated by hemorrhage and vascular leak and shock syndrome in small percentage of cases; chikungunya infections can cause persistent disabling joint symptoms, especially in older individuals; Zika has been associated with microcephaly in infants born to mothers infected during pregnancy as well as Guillain-Barre and other neurologic complications.

AC C

Education challenges are enormous for health care workers and for the general public. Individuals will need accurate and up-to-date information about risks and personal protective measure they can take. The role of Aedes and the use of repellents and personal protection The triple threat - two flaviviruses (dengue and Zika) and one alphavirus – share the same primary Aedes mosquito vector. About 950 species of Aedes (Stegomyia) exist worldwide. Aedes aegypti, is widely distributed in Rio de Janeiro and elsewhere in Brazil. Aedes aegypti is abundant in densely populated urban centers and has demonstrated its prowess in spreading the dengue virus – more than 1.6 million suspect and confirmed cases of dengue were reported in Brazil in 2015. Aedes albopictus, the Asian tiger mosquito, is also present in many areas of Brazil and has been the primary vector in outbreaks of dengue and chikungunya infections elsewhere including Europe. Although it is less strongly attracted to the human habitat and human blood than Aedes aegypti, it can survive a wider range of temperatures and habitats (including forested areas), making it a potential bridge vector for other viruses. Aedes species are typically day-time

3

ACCEPTED MANUSCRIPT

biters with a preference for crepuscular periods (dawn and dusk). Vector knowledge is essential for optimal use of preventive measures particularly in the context of public health measures (reduction of mosquito breeding sites, use of pesticides and insecticides and population education).

AC C

EP

TE D

M AN U

SC

RI PT

On an individual level, personal protection measures are key for travellers visiting areas with DENV, CHIKV and ZIKV transmission. Because there are no vaccines (except for dengue – a dengue vaccine has recently been registered in Brazil) and because no specific treatments are available for these arboviral infections, use of repellents is particularly important. Female Aedes mosquitoes have a strong drive to bite as they require a blood meal for egg production. The mosquitoes can localize targets at a distance of about 50-100 m and are initially attracted by movement and colour. Closer to the target mosquitoes are attracted by a variety of olfactory cues mainly products produced by human metabolism or the bacterial degradation of sweat components. Strong attractants include lactic acid and and 1-octen-3-ol [9]. Carbon dioxide from breath has been shown to sensitize Aedes mosquitoes to human skin odours (10). A repellent is defined as a chemical volatile substance that induces arthropods to move in the opposite direction from its source, ie the site of repellent application and repellents can play a key role in mosquito approach, landing and biting. Each repellent interacts with specific mosquito receptors leading to deterrent effects (11). The more effective and long lasting a repellent is, the higher the level of protection. A systematic review evaluated available repellents with regard to protective efficacy (% in a time interval) and complete protection time on human skin (12). In this review, an Aedes subspecies difference in biting behavior was noted. Ae. aegypti was shown to be a more aggressive biter and more difficult to repel than Ae albopictus. A recent controlled olfactometer study, using human hands as attractants, confirmed this deduction and showed that Ae albopictus was less strongly attracted to human hands than Ae aegypti (13). DEET (N,NDiethyl-3-Methylbenzamide) at concentrations of 20% or more, showed the highest efficacy and longest protection period (up to 10 hours). Although Icaridin [also known as Picaridin] and IR 3535 (ethyl-butylacetyl-amino-propionat, EBAAP) showed good repellency against Aedes, their efficacy was, on average, inferior to that provided by DEET (12). Eucalyptus citriodora repellency against Aedes was lower and frequent applications were required. These conclusions from the systematic review were confirmed in a newer olfactometer controlled study where the authors concluded that DEET repellents had a better repellency against Aedes over a longer time period (13). DEET repellents have been available since the 1950’s and have been extensively studied and are considered safe when used correctly (14). Concentrations of between 20 and 25% have been most frequently evaluated and DEET concentrations between 19% and 25% gave 3-9.7 hours of complete protection against Ae aegypti in the laboratory (12). Increasing the concentration of DEET to over 30% is not recommended as repellents are water soluble and frequent application (after sweating or bathing) rather than high concentrations are to be recommended for practical and safety reasons. For daytime use of repellents, sunscreen should be applied first and when this is absorbed, repellent should then be applied. Vitamin B 1(thiamine) has often been reputed to reduce human attractiveness for mosquitoes and thereby exert a protective effect. The controlled evaluation of transdermal delivery of Vitamin B1 using skin patches did not show any repellency against Ae aegypti or Ae albopictus (13)and travellers should be advised against the use of such patches.

4

ACCEPTED MANUSCRIPT

SC

RI PT

In the context of Zika prevention for pregnant women, the safety of repellents in pregnancy is a controversial topic with few well controlled studies. DEET (1.7g/day) use in pregnancy has been evaluated by McGready et al (2001) in a double blind randomized trial in the second and third trimester of pregnancy [15]. DEET crossed the placenta and was detected in 8% of blood cord samples. No adverse effects on survival, growth or development were detected in follow up lasting one year and it was concluded that DEET use is safe in later pregnancy. We found no controlled studies on DEET use in the first trimester of pregnancy and repellent use in early pregnancy is a topic that requires urgent, further study especially in the context of Zika infection. One case control study explored the use of repellents and the risk of hypospadias and found an increased odds ratio (OR 1.81) for the use of insect repellent during the first trimester [16]. Innovative approaches to evaluate this ethically challenging subject are needed such as using urinary biomarkers of repellents and insecticides to mark pregnancy exposure in epidemiological studies [17]. Because of the importance of public perception on the safety of interventions such as repellent use in pregnancy, key, evidence-based messages are needed.

EP

REFERENCES

TE D

M AN U

Public health authorities are thus challenged to provide evidence-based recommendations for travellers visiting Brazil in view of the triple arboviral threat explored in this special issue of Travel Medicine and Infectious Disease. Should pregnant women or those planning pregnancy defer travel to this area? Should men returning from Brazil with possible exposure to Zika infection refrain from unprotected sex in view of possible sexual transmission of the virus [4]? Which repellent is best? Should wide spread use of repellents in the first trimester be advocated despite a paucity of scientific studies on safety? What is the role and utility of other personal protective measures such as the use of permethrin- impregnated clothing, long clothing, air conditioning and screening? Risk and prevention of arboviral infections have major significance for travellers in general and in particular for athletes participating in the Rio Olympics and Paralympics because breathing and sweating are central activities in the games and are key attractants for Aedes mosquitoes.

AC C

1. Oehler E, Watrin L, Larre P, Leparc-Goffart I, Lastere S, Valour F, et al. Zika virus infection complicated by Guillain-Barre syndrome--case report, French Polynesia, December 2013. Euro Surveill. 2014;19(9):20720. DOI: 10.2807/15607917.ES2014.19.9.20720 PMID: 24626205 2. Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med. 2009;360(24):2536-43. DOI: 10.1056/NEJMoa0805715 PMID: 19516034 3. Campos GS, Bandeira AC, Sardi SI. Zika virus outbreak, Bahia, Brazil. Emerg Infect Dis 2015;21(Oct):1885-86. 4. Musso D, Roche C, Robin E, Nhan T, Teissier A, Cao-Lormeau VM. Potential sexual transmission of Zika virus. Emerg Infect Dis. 2015;21(2):359-61. DOI: 10.3201/eid2102.141363 PMID: 25625872

5

ACCEPTED MANUSCRIPT

5. Teixeira MG, Andrade AMS, Costa MdCN, Castro JSM, Oliveira FLS, Boes CSB, et al. East/Central/South African genotype chikungunya virus, Brazil, 2014. Emerg Infect Dis 2015;21(5):906-908. DOI:http://dx.doi.org/10.3201/eid2105.141727

RI PT

6. Wilson ME, Chen LH, Han PV, Keystone JS, Cramer JP, Segurado A, Hale DV, Jensenius M, Schwartz E, von Sonnenberg F, Leder K for the GeoSentinel Surveillance Network. Illness in travelers returned from Brazil: The GeoSentinel experience and implications for the 2014 World Cup and the 2016 summer Olympic Games. Clin Infect Dis 2014;58(15 May):1347-56. DOI: 10.1093/cid/ciu122

SC

7. Wilson ME, Chen LH. Health risks among travelers to Brazil: implications for the 2014 FIFA World Cup and 2016 Olympic Games. Travel Med Infect Dis. 2014 May-Jun;12(3):205-7. doi: 10.1016/j.

M AN U

8. Cardoso CW, Paploski IAD, Kikuti M, Rodrigues MS, Silva MMO, Campos GS, Outbreak of exanthematous illness associated with Zika, chikungunya, and dengue viruses, Salvador, Brazil. Emerg Infect Dis. 2015;21:2274–6. 9. Zwiebel L. J., Takken W.. 2004. Olfactory regulation of mosquito-host interactions. Insect Biochem. Mol. Biol. 34: 645–652

TE D

10. Dekker T, Geier M, Cardé RT. Carbon dioxide instantly sensitizes female yellow fever mosquitoes to human skin odours. J Exp Biol. 2005 Aug;208(Pt 15):2963-72. PMID: 16043601 11. Xu P., Choo Y. M., De La Rosa A., Leal W. S.. 2014. Mosquito odorant receptor for DEET and methyl jasmonate. Proc. Natl. Acad. Sci. USA. 111: 16592–16597

EP

12. Lupi E., Hatz C., Schlagenhauf P. 2013. The efficacy of repellents against Aedes, Anopheles, Culex and Ixodes spp.—a literature review. Travel Med. Infect. Dis. 11: 374– 411

AC C

13. Rodriguez SD, Drake LL, Price DP, Hammond JI, Hansen IA. The efficacy of some commercially available insect repellents for Aedes aegypti (Diptera:Culcidae) and Aedes albopictus (Diptera:Culcidae). 2015. J Insec Sci (15)1: 140 DOI:10.1093/jisesa/iev125 14. Sudakin D. L., Trevathan W. R.. 2003. DEET: a review and update of safety and risk in the general population. J. Toxicol. Clin. Toxicol. 41: 831–839 15. McGready R, Hamilton KA, Simpson JA, Cho T, Luxemburger C, Edwards R, Looareesuwan S, White NJ, Nosten F, Lindsay SW Safety of the insect repellent N,Ndiethyl-M-toluamide (DEET) in pregnancy. Am J Trop Med Hyg. 2001 Oct;65(4):285-9. 16. Dugas J1, Nieuwenhuijsen MJ, Martinez D, Iszatt N, Nelson P, Elliott P, 2010 Use of biocides and insect repellents and risk of hypospadias. Occup Environ Med. Mar;67(3):196-200. doi: 10.1136/oem.2009.047373. Epub 2009 Dec 1.

6

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

17. Lewis RC, Cantonwine DE, Anzalota Del Toro LV, Calafat AM, Valentin-Blasini L, Davis MD, Baker SE, Alshawabkeh AN, Cordero JF, Meeker JD. Urinary biomarkers of exposure to insecticides, herbicides, and one insect repellent among pregnant women in Puerto Rico. Environ Health. 2014 Nov 19;13:97. doi: 10.1186/1476-069X-13-97

7

Aedes and the triple threat of DENV, CHIKV, ZIKV--Arboviral risks and prevention at the 2016 Rio Olympic games.

Aedes and the triple threat of DENV, CHIKV, ZIKV--Arboviral risks and prevention at the 2016 Rio Olympic games. - PDF Download Free
941KB Sizes 0 Downloads 9 Views